Effects of Graded Hypothermia on Hypoxic-ischemic Brain Damage in the Neonatal Rat

Objective To investigate the effect of graded hypothermia on neuropathologic alterations of neonatal rat brain after exposed to hypoxic-ischemic insult at 37℃,33℃,31℃,and 28℃,respectively,and to observe the effect of hypothermia on 72-kDa heat shock protein (HSP72) expression after hypoxic-ischemic insult.Methods Seven days old Wistar rats were subjected to unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 2 hours at 37℃,33°C,31℃,and 28℃,respectively.The brain temperature was monitored indirectly by inserting a mini-thermocouple probe into the temporal muscle during hypoxia.After hypoxia-ischemia their mortality was assessed.Neuronal damage was assessed with HE staining 72 hours after hypoxia.HSP72 expression at 0.5,24,and 72 hours of recovery was immunohis-tochemically assessed using a monoclonal antibody to HSP72.Results Hypoxia-ischemia caused 10.5% (2/19) of mortality in rat of 37°C group,but no death occurred in 33℃,31℃ or 28℃ groups.HE staining showed neuropathologic damage was extensive in rats exposed to hypoxia-ischemia at 37℃ (more than 80.0%).The incidence of severe brain damage was significantly decreased in 33℃ (53.3%) and 31℃ groups (44.4%),and no histologic injury was seen in the 28℃ group of rats.Expression of HSP72 was manifest and persistent in the rat brain of 37°C group,but minimum in the rat brain of 28℃ group.Conclusion Mild and moderate hypothermia might prevent cerebral visible neuropathologic damage associated with hypoxic-ischemic injury by decreasing stress response.